Abstract
ObjectiveTo identify correlates and longitudinal changes in circulating antimüllerian hormone (AMH) levels as a marker of ovarian primordial follicle recruitment in normal peripubertal girls.DesignObservational study using mixed longitudinal and cross-sectional analyses.SettingNot applicable.Patient(s)Unselected girls assessed at ages 7–11 years.Intervention(s)None.Main Outcome Measure(s)AMH, inhibin B, and FSH levels were analyzed in blood samples collected at ages 7, 9, and 11 years for longitudinal analyses and at age 8 years for cross-sectional analyses.Result(s)In the cross-sectional analysis, AMH levels at age 8 years were lower in pubertal girls (median 25.0 pmol/L, interquartile range [IQR] 16.0–33.9; n = 39) than in prepubertal girls (33.5 pmol/L, IQR 22.3–49.1; n = 342). In prepubertal girls, higher AMH levels were associated with higher inhibin B levels, lower FSH levels, and larger body mass index at age 8 years and subsequently with later age at menarche. AMH levels were unrelated to birth weight or birth length. In the longitudinal analysis, AMH levels increased between ages 7 (median 27.0 pmol/L, IQR 19.2–34) and 9 years (32.0 pmol/L, IQR 26.5–42.7), then declined between 9 and 11 years (26.5 pmol/L, IQR 19–42.25) with high intraindividual correlation in AMH levels between ages 7 and 9 years and 7 and 11 years.Conclusion(s)Measurement of circulating AMH and inhibin B levels suggests that the rate of ovarian primordial follicle recruitment increases in the prepubertal years then declines again following the onset of puberty as follicular activity pattern changes.
Highlights
In 381 girls at age 8 years, median antimu€llerian hormone (AMH) levels were lower in the 39 girls with self-reported pubertal breast development (25.0 pmol/L, interquartile range [IQR] 16.0–33.9) than in 342 prepubertal girls (33.5 pmol/L, IQR 22.3–49.1; P< .0001; Fig. 1)
It is not possible to say whether a gradual increase in ovarian follicle activity facilitates or even triggers the onset of puberty, but the concept is plausible
Prepubertal Rise in AMH Levels Our observation of a longitudinal 20% rise in AMH levels during the 2 years between ages 7 and 9 years is consistent with the inferred doubling in AMH levels between ages 4 and 8 years in cross-sectional data [5,6,7]
Summary
To identify correlates and longitudinal changes in circulating antimu€llerian hormone (AMH) levels as a marker of ovarian primordial follicle recruitment in normal peripubertal girls. Conclusion(s): Measurement of circulating AMH and inhibin B levels suggests that the rate of ovarian primordial follicle recruitment increases in the prepubertal years declines again following the onset of puberty as follicular activity pattern changes. In a large sample of normal girls, we aimed to identify the hormonal and growth-related correlates of the rate of ovarian primordial follicle recruitment during peripuberty at age 8 years with the use of AMH as a marker of such activity. In a longitudinal study on a smaller number of subjects, we explored the temporal changes and degree of intraindividual tracking in AMH levels (as a marker of follicular recruitment activity) and inhibin B levels (as a marker of follicular development activity) in the peripubertal years
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